Trial to Compare the Effects of Tibolone (Livial®) and Continuous Combined Low-Dose Estradiol/Noresterone (Activelle®)

NCT00431093 | Completed Phase 4

• 2 other identifiers: P06673C-1755
• Study Type: interventional
• Target: 570
• Locations: 0 countries
• Sites: N/A

Brief Summary

The present trial is undertaken to compare the effects of Tibolone with a low-dose HRT regimen.

Conditions

Menopause

Outcome Measures

Primary Outcomes (1)

• For the bleeding evaluation, subject will be given a diary card to record the days on which no bleeding, vaginal spotting or bleeding occurs

  starting from baseline and during the whole trial period.

Secondary Outcomes (5)

• Hot flushes recorded on a daily diary card during the whole trial period.

  Entire trial

• A mammography to assess breast density and blood samples to determine the changes in endocrine parameters.

  screening and week 48

• A vaginal smear to assess the Vaginal Maturation Index and the Karyopycnotic Index results

  Baseline and week 48

• Urogenital complaints assessed with the Local Urogenital Complaints Rating Scale.

  At baseline, week 12, week 24 and week 48

• Health-related quality of life measured with the Women's Health Questionnaire 36-items (WHQ-36) the McCoy Female Sexuality Questionnaire-Short Form 9-items (MFSQ-SF) collecting prospectively medical resources utilization items

  At baseline and week 48

Study Arms (2)

1

EXPERIMENTAL

tibolone

Drug: low-dose estradiol/noresterone

2

ACTIVE COMPARATOR

low-dose estradiol/noresterone

Drug: tibolone

Interventions

tibolone DRUG

uncoded tablets, at a dose of 2.5 mg per tablet; Subjects were to take 1 Livialâ tablet and 1 -matched Activelleâ placebo tablet, orally, once a day (preferably at the same time).

Also known as: Livial

2

low-dose estradiol/noresterone DRUG

Activelleâ, estradiol (E2) 1 mg and norethisterone acetate (NETA) 0.5 mg per tablet, was supplied as uncoded tablets. Subjects were to take 1 Activelleâ tablet and 1 Livialâ-matched placebo tablet, orally, once a day (preferably at the same time).

Also known as: Activelle®

1

Eligibility Criteria

• Age: 45 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be healthy and postmenopausal women, \>= 45 and \< 65 years of age, with an intact uterus.
• Subjects must have been postmenopausal for less than 15 years.
• Body Mass Index \>18 and =\< 32 kg/m2.
• Voluntary written informed consent is required.

You may not qualify if:

• Any unexplained abnormal uterine bleeding after the menopause.
• Double layer endometrial thickness = 6 mm as assessed by transvaginal ultrasonography.
• Treatment with oral estrogen and/or progestogen therapy within 4 weeks prior to screening, or treatment with transdermal therapy and local estrogen applications within 4 weeks prior to screening.
• Any previous or current unopposed estrogen administration, prior use of estrogen pellets or tamoxifen citrate (occasional use of estrogen-containing vaginal cream is allowed after the appropriate wash-out period is completed). Estrogen combined with sequential administration of progestogen should have been at least 10 days per 28 day cycle.
• The following wash-out periods apply:
• weeks for transdermal hormonal treatment, local estrogen applications or other non-hormonal medication known to act on the relief of vasomotor symptoms (e.g. clonidine)
• weeks for phytoestrogens, tibolone, intra-uterine or oral progestogen and oral estrogen/progestogen therapy
• months for progestogen implants or injections and estrogen/progestogen injectable therapy.
• Any serious disease or disorder; or any endocrine disorder; (controlled hypo/hyperthyroidism and diabetes mellitus Type II is allowed).
• Diseases for which exogenous hormonal steroids are contraindicated.
• History or presence of any malignancy, except successfully treated nonmelanoma skin cancers.
• History or presence of cardiovascular or cerebrovascular conditions:
• thrombophlebitis, thrombosis or thromboembolic disorders.
• History or presence of liver, gallbladder (subjects who have had a cholecystectomy will not be excluded) or renal disease, epilepsy or classical migraine headaches.
• History or presence of clinically significant depression or other psychiatric disorders which, in the investigator's judgment, might compromise or confound the subject's participation in the trial.

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Hammar ML, van de Weijer P, Franke HR, Pornel B, von Mauw EM, Nijland EA; TOTAL Study Investigators Group. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. BJOG. 2007 Dec;114(12):1522-9. doi: 10.1111/j.1471-0528.2007.01537.x.

  PMID: 17995496 DERIVED

MeSH Terms

Interventions

tibolone; Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2007
• First Posted: February 5, 2007
• Study Start: November 1, 2002
• Primary Completion: March 1, 2005
• Study Completion: March 1, 2005
• Last Updated: February 3, 2022

Record last verified: 2022-02